Incidence and Predictors of Progression to Chagas Cardiomyopathy: Long-Term Follow-Up of <i>Trypanosoma cruzi</i>-Seropositive Individuals.

Abstract

There are few contemporary cohorts of <i>Trypanosoma cruzi</i>-seropositive individuals, and the basic clinical epidemiology of Chagas disease is poorly understood. Herein, we report the incidence of cardiomyopathy and death associated with <i>T. cruzi</i> seropositivity. Participants were selected in blood banks at 2 Brazilian centers. Cases were defined as <i>T. cruzi</i>-seropositive blood donors. <i>T. cruzi</i>-seronegative controls were matched for age, sex, and period of donation. Patients with established Chagas cardiomyopathy were recruited from a tertiary outpatient service. Participants underwent medical examination, blood collection, ECG, and echocardiogram at enrollment (2008-2010) and at follow-up (2018-2019). The primary outcomes were all-cause mortality and development of cardiomyopathy, defined as the presence of a left ventricular ejection fraction <50% or QRS complex duration ≥120 ms, or both. To handle loss to follow-up, a sensitivity analysis was performed using inverse probability weights for selection. We enrolled 499 <i>T. cruzi</i>-seropositive donors (age 48±10 years, 52% male), 488 <i>T. cruzi</i>-seronegative donors (age 49±10 years, 49% male), and 101 patients with established Chagas cardiomyopathy (age 48±8 years, 59% male). The mortality in patients with established cardiomyopathy was 80.9 deaths/1000 person-years (py) (54/101, 53%) and 15.1 deaths/1000 py (17/114, 15%) in <i>T. cruzi</i>-seropositive donors with cardiomyopathy at baseline. Among <i>T. cruzi</i>-seropositive donors without cardiomyopathy at baseline, mortality was 3.7 events/1000 py (15/385, 4%), which was no different from <i>T. cruzi</i>-seronegative donors with 3.6 deaths/1000 py (17/488, 3%). The incidence of cardiomyopathy in <i>T. cruzi</i>-seropositive donors was 13.8 (95% CI, 9.5-19.6) events/1000 py (32/262, 12%) compared with 4.6 (95% CI, 2.3-8.3) events/1000 py (11/277, 4%) in seronegative controls, with an absolute incidence difference associated with <i>T. cruzi</i> seropositivity of 9.2 (95% CI, 3.6-15.0) events/1000 py. <i>T. cruzi</i> antibody level at baseline was associated with development of cardiomyopathy (adjusted odds ratio, 1.4 [95% CI, 1.1-1.8]). We present a comprehensive description of the natural history of <i>T. cruzi</i> seropositivity in a contemporary patient population. The results highlight the central importance of anti-<i>T. cruzi</i> antibody titer as a marker of Chagas disease activity and risk of progression.